Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy primarily of the right ventricle characterized through fibrofatty replacement of cardiomyocytes. The genetic etiology in ARVC patients is most commonly caused by dominant inheritance and high genetic heterogeneity. Though histological examinations of ARVC affected human myocardium reveals fibrolipomatous replacement, the molecular mechanisms leading to loss of cardiomyocytes are largely unknown.
Myocardial transcriptome analysis of human arrhythmogenic right ventricular cardiomyopathy.
Sex, Age
View SamplesMechanical unloading by ventricular assist devices (VAD) leads to significant gene-expression changes often summarized as reverse remodeling. However, little is known on individual transcriptome changes during VAD-support and its relationship to non-failing hearts (NF). In addition no data are available for the transcriptome regulation during non-pulsatile VAD-support. Therefore we analysed the gene-expression patterns of 30 paired samples from VAD-supported (including 8 non-pulsatile VADs) and 8 non-failing control hearts (NF) using the first total human genome-array available.
Global gene expression analysis in nonfailing and failing myocardium pre- and postpulsatile and nonpulsatile ventricular assist device support.
Sex, Age, Specimen part, Disease
View SamplesTranscript profiling analysis of csn4-1 light grown mutant seedlings compared to wild type using Arabidopsis ATH1 GeneChip array
Characterization of the VIER F-BOX PROTEINE genes from Arabidopsis reveals their importance for plant growth and development.
No sample metadata fields
View SamplesWe used microarrays to detail the global gene expression changes following apical infection of porcine choroid plexus epithelial cells (PCPEC) with Streptococcus suis (S. suis)
In vitro transcriptome analysis of porcine choroid plexus epithelial cells in response to Streptococcus suis: release of pro-inflammatory cytokines and chemokines.
Specimen part
View SamplesConditional ablation of Ezh2 in the neural crest lineage results in loss of the neural crest-derived mesenchymal derivatives. In this data sheet we determine gene expression analysis in Ezh2lox/lox and Wnt1Cre Ezh2lox/lox in E11.5 mouse BA1 cells.
Ezh2 is required for neural crest-derived cartilage and bone formation.
Specimen part
View SamplesGenome-wide association studies (GWAS) have identified dozens of genomic loci, whose single nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the biological functions of these common genetic variants and the mechanisms to increase disease risk are largely unknown. We integrated chromatin-IP coupled sequencing (ChIP-seq) and microarray expression profiling in the TMPRSS2-ERG gene rearrangement positive DuCaP cell model with the NHGRI GWAS PCa risk SNPs catalog, in an attempt to identify disease susceptibility SNPs localized within functional androgen receptor binding sites (ARBSs). Among the 48 GWAS index SNPs and 2,702 linked SNPs defined by the 1000G project 104 were found to be localized in the AR ChIP-seq peaks. Of these risk SNPs, rs11891426 T/G in the 7th intron of its host gene melanophilin (MLPH) was found located within a putative auxiliary ARE motif, which we found enriched in the neighborhood of canonical ARE motifs. Exchange of T to G attenuated the transcriptional activity of the MLPH-ARBS in a reporter gene assay. The expression of MLPH protein in tissue samples from prostate cancer patients was significantly lower in those with the G compared to the T allele. Moreover, a significant positive correlation of AR and MLPH protein expression levels was also confirmed in tissue samples. These results unravel a hidden link between AR and a functional PCa risk SNP rs11891426, whose allele alteration affects androgen regulation of its host gene MLPH. This study shows the power of integrative studies to pin down functional risk SNPs and justifies further investigations.
Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.
Cell line, Treatment, Time
View SamplesTransplanting renal allografts represents the major curative treatment of chronic renal failure. Despite recent advances in immunosuppressive therapy, long-term survival of allografts remains a major clinical problem. Kidney function depends in part on transport proteins such as MRP2 (ABCC2) which facilitates renal secretion of amphiphilic exogenous and endogenous compounds. Inherited variants of genes not related to the immune system have been shown to modify the outcome after renal transplantation. We investigated whether ABCC2 gene variants in the donor kidney affect renal graft function.
Multidrug resistance-related protein 2 genotype of the donor affects kidney graft function.
Sex
View SamplesWe report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts. We find that lysine 4 and lysine 27 trimethylation effectively discriminates genes that are expressed, poised for expression, or stably repressed, and therefore reflect cell state and lineage potential. Lysine 36 trimethylation marks primary coding and non-coding transcripts, facilitating gene annotation. Trimethylation of lysine 9 and lysine 20 is detected at satellite, telomeric and active long-terminal repeats, and can spread into proximal unique sequences. Lysine 4 and lysine 9 trimethylation marks imprinting control regions. Finally, we show that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms. This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations. Overall design: GMP and MEP were isolated from Runx1+/+-Tg(vav-Cre) and Runx1fl/fl-Tg(vav-Cre) mice as well as Runx1fl/fl-Tg(vav-Cre) XMP, total RNA extracted and sequenced
Runx1 downregulates stem cell and megakaryocytic transcription programs that support niche interactions.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB.
Cell line
View SamplesTo gain global insights into the role of the well-known repressive splicing regulator PTB we analyzed the consequences of PTB knockdown in HeLa cells using high-density oliogonucleotide splice-sensitive microarrays. The major class of identified PTB-regulated splicing event was PTB-repressed cassette exons, but there was also a substantial number of PTB-activated splicing events. PTB repressed and activated exons showed a distinct arrangement of motifs with pyrimidine-rich motif enrichment within and upstream of repressed exons, but downstream of activated exons. The N-terminal half of PTB was sufficient to activate splicing when recruited downstream of a PTB-activated exon. Moreover, insertion of an upstream pyrimidine tract was sufficient to convert a PTBactivated to a PTB-repressed exon. Our results demonstrate that PTB, an archetypal splicing repressor, has variable splicing activity that predictably depends upon its binding location with respect to target exons.
Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB.
Cell line
View Samples